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Hyperendemic pulmonary tuberculosis in peri-urban areas of Karachi, Pakistan
Saeed Akhtar, Franklin White, Rumina Hasan, Shafquat Rozi, Mohammad Younus, Faiza Ahmed, Sara Husain, Bilquis Khan
BMC Public Health , 2007, DOI: 10.1186/1471-2458-7-70
Abstract: A cross-sectional study was conducted in two peri-urban neighbourhoods from May 2002 to November 2002. Systematic sampling design was used to select households for inclusion in the study. Consenting subjects aged 15 years or more from selected households were interviewed and, whenever possible, sputum samples were obtained. Sputum samples were subjected to direct microscopy by Ziehl-Neelson method, bacterial culture and antibiotic sensitivity tests.The prevalence (per 100,000) of pulmonary tuberculosis among the subjects aged 15 years or more, who participated in the study was 329 (95% confidence interval (CI): 195 – 519). The prevalence (per 100,000) of pulmonary tuberculosis adjusted for non-sampling was 438 (95% CI: 282 – 651). Other than cough, none of the other clinical variables was significantly associated with pulmonary tuberculosis status. Analysis of drug sensitivity pattern of 15 strains of Mycobacterium tuberculosis revealed that one strain was resistant to isoniazid alone, one to streptomycin alone and one was resistant to isoniazid and streptomycin. The remaining 12 strains were susceptible to all five drugs including streptomycin, isoniazid, rifampicin, ethambutol, and pyrazinamide.This study of previously undetected tuberculosis cases in an impoverished peri-urban setting reveals the poor operational performance of Pakistan's current approach to tuberculosis control; it also demonstrates a higher prevalence of pulmonary tuberculosis than current national estimates. Public health authorities may wish to augment health education efforts aimed at prompting health-seeking behaviour to facilitate more complete and earlier case detection. Such efforts to improve passive case-finding, if combined with more accessible DOTS infra-structure for treatment of detected cases, may help to diminish the high tuberculosis-related morbidity and mortality in marginalized populations. The economics of implementing a more active approach to case finding in resource-const
Drug Resistance among Pulmonary Tuberculosis Patients in Calabar, Nigeria  [PDF]
Akaninyene Otu,Victor Umoh,Abdulrazak Habib,Soter Ameh,Lovett Lawson,Victor Ansa
Pulmonary Medicine , 2013, DOI: 10.1155/2013/235190
Abstract: Background. This study aimed to determine the pattern of drug susceptibility to first-line drugs among pulmonary TB patients in two hospitals in Calabar, Nigeria. Methods. This was a descriptive cross-sectional study carried out between February 2011 and April 2012. Sputum samples from consecutive TB patients in Calabar were subjected to culture on Lowenstein-Jensen (LJ) slopes followed by drug susceptibility testing (DST). The DST was performed on LJ medium by the proportion method. Results. Forty-two of the 100 Mycobacterium tuberculosis strains were found to be resistant to at least one drug. Resistance to only one drug (monoresistance) was found in 17 patients. No strains with monoresistance to rifampicin were found. Resistance to two drugs was found in 22 patients, while one patient was resistant to both three and four drugs. MDR TB was seen in 4% (4/100). The independent variables of HIV serology and sex were not significantly associated with resistance ( ). Conclusion. There was a high prevalence of anti-TB drug resistance in Calabar. 1. Introduction Tuberculosis (TB), an ancient infectious disease caused by Mycobacterium tuberculosis, is the leading cause of death due to an infectious agent globally. It is both preventable and treatable [1, 2]. The World Health Organization (WHO) records an average of nine million new TB cases annually and about 5000?TB deaths daily [1]. TB and human immunodeficiency virus (HIV) coinfection and the exponential increase in drug resistance are greatly responsible for the resurgence of TB [3]. Other identified factors include neglect of TB control by governments, poor management of programmes, poverty, population growth, and rapid uncontrolled urbanization [4]. Drug-resistant TB is a case of TB (usually pulmonary) excreting bacilli resistant to one or more anti-TB drugs [5]. Acquired drug resistance results from exposure to a single drug due to irregular drug supply, inappropriate prescription, or poor adherence to treatment. This suppresses the growth of bacilli susceptible to that drug while permitting multiplication of drug-resistant organisms. Primary or initial drug resistance occurs when such drug resistant bacilli are transmitted to other people [5]. Resistance to one anti-TB drugs is known as mono resistance. Poly resistance is resistant to two or more anti-TB drugs, but not to both isonazid & rifampicin. Multidrug-resistant TB (MDR TB) is resistant to at least isoniazid and rifampicin, the two key first-line anti-TB drugs in short course chemotherapy [5]. These forms of TB do not respond to the standard
Phenotypic characterisation and drug sensitivity testing of mycobacteria isolated from extra-pulmonary tuberculosis  [PDF]
R Gurung,SK Bhattacharya,B Pradhan,S Gurung,YI Singh
Kathmandu University Medical Journal , 2010, DOI: 10.3126/kumj.v8i1.3223
Abstract: Background: Tuberculosis (TB) is a major cause of morbidity and mortality globally, with most cases occurring in developing countries. The importance of extra pulmonary tuberculosis (EPTB) among all forms of tuberculosis has not yet been ascertained in developing countries Objective: To identify and perform phenotypic characterization of clinically important mycobacterium isolates from extra-pulmonary sites along with drug susceptibility testing. Materials and methods: A total of 513 specimens from patients of (EPTB) with varied presentation were studied. Speciation and characterization of isolates were done on the basis of growth and biochemical characteristics. Drug susceptibility testing for mycobacterium isolates was done by proportion method. Results: Fifty four patients clinically suspected to have extra-pulmonary tuberculosis were culture positive for mycobacteria. On characterization 48 of the 54 isolates were identified as M. tuberculosis, 4 as M. bovis and 2 were M. avium/ intracelulare. Drug susceptibility testing was done for the both M. tuberculosis as well as M. bovis. In single drug resistance, Streptomycin was highest followed by Isoniazid, Ethambutol and Refampicin. Multi drug resistance (MDR) was found in 6 isolates and it was observed only in group I cases. Conclusion: EPTB accounts for 10-15 percent of all cases of tuberculosis. Mycobacterium was present in 10.5 percent samples. 48 isolates out of 54 samples were found to be M. tuberculosis. The maximum numbers of M. tuberculosis were isolated from lymph node aspiration. Key words: Phenotypic characterization; drug susceptibility; extra pulmonary tuberculosis DOI: 10.3126/kumj.v8i1.3223 Kathmandu University Medical Journal (2010), Vol. 8, No. 1, Issue 29, 57-61
Tuberculosis Recurrence and Mortality after Successful Treatment: Impact of Drug Resistance  [PDF]
Helen Cox ,Yared Kebede,Sholpan Allamuratova,Gabit Isov,Zamira Davletmuratova,Graham Byrnes,Christine Stone,Stefan Niemann,Sabine Rüsch-Gerdes,Lucie Blok,Daribay Doshetov
PLOS Medicine , 2006, DOI: 10.1371/journal.pmed.0030384
Abstract: Background The DOTS (directly observed treatment short-course) strategy for tuberculosis (TB) control is recommended by the World Health Organization globally. However, there are few studies of long-term TB treatment outcomes from DOTS programs in high-burden settings and particularly settings of high drug resistance. A DOTS program was implemented progressively in Karakalpakstan, Uzbekistan starting in 1998. The total case notification rate in 2003 was 462/100,000, and a drug resistance survey found multidrug-resistant (MDR) Mycobacterium tuberculosis strains among 13% of new and 40% of previously treated patients. A retrospective, observational study was conducted to assess the capacity of standardized short-course chemotherapy to effectively cure patients with TB in this setting. Methods and Findings Using routine data sources, 213 patients who were sputum smear-positive for TB, included in the drug resistance survey and diagnosed consecutively in 2001–2002 from four districts, were followed up to a median of 22 months from diagnosis, to determine mortality and subsequent TB rediagnosis. Valid follow-up data were obtained for 197 (92%) of these patients. Mortality was high, with an average of 15% (95% confidence interval, 11% to 19%) dying per year after diagnosis (6% of 73 pansusceptible cases and 43% of 55 MDR TB cases also died per year). While 73 (74%) of the 99 new cases were “successfully” treated, 25 (34%) of these patients were subsequently rediagnosed with recurrent TB (13 were smear-positive on rediagnosis). Recurrence ranged from ten (23%) of 43 new, pansusceptible cases to six (60%) of ten previously treated MDR TB cases. MDR M. tuberculosis infection and previous TB treatment predicted unsuccessful DOTS treatment, while initial drug resistance contributed substantially to both mortality and disease recurrence after successful DOTS treatment. Conclusions These results suggest that specific treatment of drug-resistant TB is needed in similar settings of high drug resistance. High disease recurrence after successful treatment, even for drug-susceptible cases, suggests that at least in this setting, end-of-treatment outcomes may not reflect the longer-term status of patients, with consequent negative impacts for patients and for TB control.
Unsuspected and extensive transmission of a drug-susceptible Mycobacterium tuberculosis strain
Ana López-Calleja, Patricia Gavín, Ma Antonia Lezcano, Ma Asunción Vitoria, Ma José Iglesias, Joaquín Guimbao, Ma ángeles Lázaro, Nalin Rastogi, Ma José Revillo, Carlos Martín, Sofia Samper
BMC Pulmonary Medicine , 2009, DOI: 10.1186/1471-2466-9-3
Abstract: The Mycobacterium tuberculosis drug-susceptible strain, named MTZ strain, was genetically characterized by IS6110-RFLP, Spoligotyping and by MIRU-VNTR typing and the genetic patterns obtained were compared with those included in international databases. The characteristics of the affected patients, in an attempt to understand why the MTZ strain was so highly transmitted among the population were also analyzed.The genetic profile of the MTZ strain was rare and not widely distributed in our area or elsewhere. The patients affected did not show any notable risk factor for TB.The M. tuberculosis strain MTZ, might have particular transmissibility or virulence properties, and we believe that greater focus should be placed on stopping its widespread dissemination.Mycobacterium tuberculosis is an extremely successful pathogen that kills nearly two million people in the world each year [1]. The study of tuberculosis (TB) epidemiology and transmission, traditionally involving patient contact tracing, has been improved by the use of molecular strain typing [2]. Molecular epidemiological studies have added much-needed accuracy and precision to the study of transmission dynamics, and have allowed previously unresolved issues to be newly addressed, e.g. the classification of recent-versus-reactive disease, the extent of exogenous reinfection and the detection of unsuspected transmission events [2].Advances in molecular typing have led to the identification of highly transmissible M. tuberculosis complex strains in the last years. In New York City, the W strain caused more than 350 cases [3] and spread to other American states [4]. A Beijing strain imported from Liberia affected 75 patients in the Gran Canaria Island during the 1990s [5]. Currently, the major threat for TB control is the transmission of extensively drug-resistant (XDR) strains [6,7]. However other strains, neither belonging to the W-Beijing family nor being drug-resistant, have shown extensive dissemination in var
Prevalence of Pulmonary Tuberculosis Among HIV Infected Drug Users in Pokhara, Kaski, Nepal  [PDF]
SC Verma,GP Dhungana,HS Joshi,HB Kunwar,RK Jha,AK Pokhrel
SAARC Journal of Tuberculosis, Lung Diseases and HIV/AIDS , 2010, DOI: 10.3126/saarctb.v7i2.4401
Abstract: Introduction: Studies conducted in different countries suggest that HIV infected drug users have a higher chance of acquiring pulmonary tuberculosis (PTB) in comparison to general population. However, there is no information about the prevalence of PTB among HIV infected drug users in Nepal. Objectives: The main objectives of this study were to document the socio-demographic and behavioral attributes; clinical symptoms and prevalence of PTB in HIV infected drug users in Pokhara, Kaski, Nepal. Methods: In a cross-sectional study, we enrolled 62 HIV infected drug users not diagnosed with PTB in the past from five HIV care centers in Pokhara. Using questionnaire, first we documented participants’ socio-demographic and behavioral attributes and clinical symptoms. This was followed by tuberculosis testing in all enrolled participants at the Regional Tuberculosis Center (RTC) in Pokhara. Results: Of the 62 HIV infected drug users, PTB was diagnosed in 3 (4.8%) participants. All of them were male in the productive age group. Cough was the major clinical symptoms (54.8%) in the study participants. About 91.9% participants reported they had acquired HIV infection through injecting drug use. Buprenorphine/heroin was the major drug used (48.4%) for addiction. Conclusion: This study provides first evidence of prevalence of PTB in HIV infected drug users in Nepal. The findings suggest tuberculosis testing be conducted in HIV infected persons including the HIV infected drug users in Nepal. Early detection of PTB in HIV infected drug users may help to reduce the morbidity and mortality as well as spread of TB in the community. Keywords: Drug users; HIV/AIDS; Nepal; Pokhara; Tuberculosis DOI: 10.3126/saarctb.v7i2.4401 SAARC J. TUBER. LUNG DIS. HIV/AIDS 2010 VII(2) 19-25
Pulmonary Tuberculosis and Drug Resistance in Dhaka Central Jail, the Largest Prison in Bangladesh  [PDF]
Sayera Banu,Arman Hossain,Mohammad Khaja Mafij Uddin,Muhammad Reaj Uddin,Tahmeed Ahmed,Razia Khatun,Asif Mujtaba Mahmud,Khurshid Alam Hyder,Afzalunnessa Binte Lutfor,Md. Sirajul Karim,Khalequ Zaman,Md. Ashraful Islam Khan,Pravat Chandra Barua,Stephen P. Luby
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0010759
Abstract: There are limited data on TB among prison inmates in Bangladesh. The aim of the study was to determine the prevalence of pulmonary tuberculosis (TB), its drug resistance and risk factors in Dhaka Central Jail, the largest prison in Bangladesh.
High frequency of first-line anti-tuberculosis drug resistance among persons with chronic pulmonary tuberculosis at a teaching hospital chest clinic
A Forson, S Kudzawu, A Kwara, T Flanigan
Ghana Medical Journal , 2010,
Abstract: Introduction: The burden of MDR-TB is unknown in areas that do not have drug susceptibility testing (DST), but its frequency is expected to be higher in previously treated cases. Where DST is not available the WHO recommended standardized retreatment (Category II) regimen is given to previously treated TB patients Objective: To evaluate the frequency and pattern of drug resistance of Mycobacterium tuberculosis isolated from patients with chronic smear positive pulmonary tuberculosis. Method: We conducted a retrospective review of mycobacterial cultures and drug susceptibility testing (DST) performed on sputum samples collected, between January 2005 and September 2006, from 40 patients with pulmonary TB who had failed at least one standard retreatment regimen. Clinical data was extracted from patients’ case notes. Results: M. tuberculosis was recovered from 28 (70%) of the 40 patients. Of the 28 culture positive cases, 10 (36%) had resistance to at least rifampicin and isoniazid (multi-drug resistant TB), 22 (79%) isolates had resistance to streptomycin and 13 (46%) to ethambutol. Of the patients with a positive culture, only one (3.6%) had a fully susceptible organism. Of the 10 patients with MDR TB, 7 had received two or more retreatment courses. Conclusion: The frequency of drug resistant TB was high among patients who failed at least one course of category II therapy. Effective combination regimens based on DST is necessary in patients who remain smear positive on the standardized retreatment regimen.
Pattern Of Drug Induced Hyperuricaemia In Nigerians With Pulmonary Tuberculosis
S.A. Adebisi, A.B. Okesina, P.O. Oluboyo
African Journal of Clinical and Experimental Microbiology , 2002,
Abstract: Thirty-one patients with newly diagnosed pulmonary tuberculosis were longitudinally studied between January 1997 and June 1998; each for 6 months to determine the pattern of drug induced hyperuricaemia. Biochemical indices determined were serum urate and 24 hours urinary output of urate, before and during treatment with antituberculosis therapy. At the end of the 1st and 2nd months of therapy 16 (51.6%) and 15 (48.4%) of the patients respectively were hyperuricaemic. These were statistically significant when compared with the pretreatment data with P value of 0.001 and 0.002 respectively. At the end of the 6th months there was no significant difference in the incidence of hyperuricaemia observed as compared with the pretreatment level. The pretreatment mean 24 hours urinary urate output was 4.83 mmol/24 hours, the corresponding values at the end of the 1st and second months of treatment was 3.38 mmol/24 hour and 3.74mmol/24 hours. These value are significantly lower than the pretreatment value with P value of P < 0.05 respectively. This however returns to the pretreatment range by the end of he 6th month of treatment with a value of 4.05 mmol/24 hours and P – value of 0.178. We concluded therefore that while hyperuricaemia is a known cause of nephropathy, the pattern of drug induced hyperuricaemia that occurs in patients with pulmonary tuberculosis is self- limiting and should therefore not hinder us from optimizing the benefits of the drugs. (Af. J. of Clinical and Experimental Microbiology: 2002 3(1): 17-20)
High Isoniazid Resistance Rates in Rifampicin Susceptible Mycobacterium tuberculosis Pulmonary Isolates from Pakistan  [PDF]
Naima Fasih, Yasraba Rafiq, Kausar Jabeen, Rumina Hasan
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0050551
Abstract: Background Rapid new diagnostic methods (including Xpert MTB/RIF assay) use rifampicin resistance as a surrogate marker for multidrug resistant tuberculosis. Patients infected with rifampicin susceptible strains are prescribed first line anti-tuberculosis therapy. The roll out of such methods raises a concern that strains with resistance to other first line anti-tuberculosis drugs including isoniazid will be missed and inappropriate treatment given. To evaluate implications of using such methods review of resistance data from high burden settings such as ours is essential. Objective To determine resistance to first line anti-tuberculosis drugs amongst rifampicin susceptible pulmonary Mycobacterium tuberculosis (MTB) isolates from Pakistan. Materials and Methods Data of pulmonary Mycobacterium tuberculosis strains isolated in Aga Khan University Hospital (AKUH) laboratory (2009–2011) was retrospectively analyzed. Antimicrobial susceptibility profile of rifampicin susceptible isolates was evaluated for resistance to isoniazid, pyrazinamide, ethambutol, and streptomycin. Results Pulmonary specimens submitted to AKUH from 2009 to 2011 yielded 7738 strains of Mycobacterium tuberculosis. These included 54% (n 4183) rifampicin susceptible and 46% (n: 3555) rifampicin resistant strains. Analysis of rifampicin susceptible strains showed resistance to at least one of the first line drugs in 27% (n:1133) of isolates. Overall isoniazid resistance was 15.5% (n: 649), with an isoniazid mono-resistance rate of 4% (n: 174). Combined resistance to isoniazid, pyrazinamide, and ethambutol was noted in 1% (n: 40), while resistance to isoniazid, pyrazinamide, ethambutol, and streptomycin was observed in 1.7% (n: 70) of strains. Conclusions Our data suggests that techniques (including Xpert MTB/RIF assay) relying on rifampicin susceptibility as an indicator for initiating first line therapy will not detect patients infected with MTB strains resistant to other first line drugs (including isoniazid). The roll out of these techniques must therefore be accompanied by strict monitoring ensuring early resistance detection to increase chances of improved patient outcomes.
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